Evidence for auto-inhibition by the N terminus of hADAR2 and activation by dsRNA binding

RNA
Mark R MacbethBrenda L Bass

Abstract

Adenosine deaminases that act on RNA (ADARs) catalyze adenosine to inosine conversion in RNA that is largely double stranded. Human ADAR2 (hADAR2) contains two double-stranded RNA binding motifs (dsRBMs), separated by a 90-amino acid linker, and these are followed by the C-terminal catalytic domain. We assayed enzymatic activity of N-terminal deletion constructs of hADAR2 to determine the role of the dsRBMs and the intervening linker peptide. We found that a truncated protein consisting of one dsRBM and the deaminase domain was capable of deaminating a short 15-bp substrate. In contrast, full-length hADAR2 was inactive on this short substrate. In addition, we observed that the N terminus, which was deleted from the truncated protein, inhibits editing activity when added in trans. We propose that the N-terminal domain of hADAR2 contains sequences that cause auto-inhibition of the enzyme. Our results suggest activation requires binding to an RNA substrate long enough to accommodate interactions with both dsRBMs.

References

Feb 1, 1988·Biophysical Chemistry·G N GiaeverJ C Wang
Nov 11, 1987·Nucleic Acids Research·J F MilliganO C Uhlenbeck
Aug 10, 1999·Journal of Molecular Biology·K A Lehmann, B L Bass
Dec 28, 1999·Analytical Biochemistry·K Melcher
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·A Herbert, A Rich
Jun 5, 2002·Annual Review of Biochemistry·Brenda L Bass
Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Daniel P MorseBrenda L Bass
Aug 7, 2002·The Journal of Biological Chemistry·Dominic C J JaikaranAndrew M MacMillan
Nov 26, 2002·The Journal of Biological Chemistry·Stefan MaasKazuko Nishikura
Mar 6, 2003·The Journal of Biological Chemistry·Dan-Sung C ChoKazuko Nishikura
Jul 4, 2003·The EMBO Journal·Angela GalloMary A O'Connell
Aug 9, 2003·Nucleic Acids Research·Annika M KällmanMarie Ohman

❮ Previous
Next ❯

Citations

Sep 24, 2005·Nucleic Acids Research·Michael KoerisStefan Maas
May 5, 2006·Molecular Biology of the Cell·Ming XuRonald B Emeson
Feb 17, 2009·Nucleosides, Nucleotides & Nucleic Acids·Prasanna JayalathPeter A Beal
Dec 25, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Cyril X GeorgeCharles E Samuel
Dec 20, 2011·Nucleic Acids Research·Thomas D GrantElizabeth J Grayhack
Aug 25, 2009·Journal of Structural and Functional Genomics·Erin QuartleyElizabeth J Grayhack
May 3, 2007·Nature Reviews. Molecular Cell Biology·Bradley M LundeGabriele Varani
Aug 1, 2009·Journal of the American Chemical Society·Subhash PokharelPeter A Beal
May 19, 2011·Nature Communications·Julie M EggingtonBrenda L Bass
Nov 25, 2011·Molecular Neurobiology·Cesare OrlandiSergio Barlati
Oct 6, 2015·Biomolecules·Niamh MannionMary A O'Connell
Jan 13, 2005·Chembiochem : a European Journal of Chemical Biology·Peter A Beal
Aug 19, 2011·The EMBO Journal·Roberto MarcucciMary A O'Connell
Sep 1, 2011·The EMBO Journal·Michael Doyle, Michael A Kiebler
Oct 7, 2011·Wiley Interdisciplinary Reviews. RNA·Helene Wahlstedt, Marie Ohman
Jun 23, 2015·Angewandte Chemie·Rena A MizrahiPeter A Beal
Apr 16, 2013·Journal of Molecular Biology·Thomas D GrantEdward H Snell
Sep 24, 2004·Chemistry & Biology·Olen M StephensPeter A Beal
Feb 14, 2006·Structure·Richard SteflFrédéric H-T Allain
Jan 8, 2015·Nucleic Acids Research·Kelly J PhelpsPeter A Beal
Aug 26, 2016·Nucleic Acids Research·Maria Fernanda Montiel-GonzálezJoshua J C Rosenthal
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ashani Kuttan, Brenda L Bass
Apr 19, 2006·The Journal of Biological Chemistry·Kaari A ChilibeckAndrew M MacMillan
Jul 1, 2020·Nucleic Acids Research·Alexander S Thuy-BounPeter A Beal
Feb 22, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Justin M Thomas, Peter A Beal
Jan 24, 2007·ACS Chemical Biology·Subhash Pokharel, Peter A Beal
Aug 10, 2006·Chemical Reviews·Olena Maydanovych, Peter A Beal
Jan 27, 2012·Genes & Development·Michael Doyle, Michael A Kiebler

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.